June, 2014

Target of Opportunity

By Michael J. Katin, MD

This month contains the centennial "celebration" of the event that set off the Great War, otherwise (and, eventually, inappropriately) known as the War to End All Wars. On June 28, 1914, Archduke Franz Ferdinand and Archduchess Sophie of the Austro-Hungarian Empire were visiting Sarajevo, in Bosnia-Herzegovina. They had been targeted for assassination by five Serbian radicals, and a bomb thrown at the motorcade bounced off the royal couple's car and injured several others in the group. The Archduke and Archduchess would have finished their time in Sarajevo and moved on safely, except that Franz Ferdinand decided to do the right thing and go back to visit the injured. This took their vehicle past Schiller's delicatessen, by which one of the five, Gavrilo Princip, who should someday be played by Johnny Depp, was hanging out. He was able to walk up to the royal couple and shoot both of them, although it is not documented as to whether he left the delicatessen without paying the bill

This episode had two major consequences. The first is that a chain of events followed that set off the bloodiest, most extensive conflict the world had yet seen (the sequence is detailed elsewhere ) The second, and more distinctive, is that this has allowed the Archduke and Archduchess to achieve (although posthumously ) the unprecedented honor of being the first husband-and-wife combination to have both pictures heading this series of columns, albeit nearly six years apart.

The Great War, as well as the past two decades of the War on Cancer, is noted for its technological advances. It is of interest that the theme of this year's ASTRO conference is "Targeting Cancer: Technology & Biology." Does this imply that previous treatment techniques were, literally, aimless? Obviously not, but, whether the results are the deaths of millions of soldiers and civilians or billions of malignant cells, certain trends appear in common. (It probably needs to be called to attention that the word "targeted" has replaced "state-of-the-art," "cutting-edge," and all the other over-used and basically meaningless adjectives previously used to hype treatment methods and facilities. The lifespan of this term may be approximately two years, after which it will undoubtedly be superseded by another emotionogenic modifier, such as "ultra-ultimate" or "gonzo.")

The 2014 annual meeting of the American Society of Clinical Oncology begins on May 30, and inexplicably and discourteously has not scheduled any recognition that June 28 is rapidly approaching. The theme for this year is "Science & Society," implying that previously there was not enough emphasis on either, although the majority of presentations deal with targeting, as did Mr. Princip. Perhaps using the slogan "Science & Society & Targeting" was considered too cumbersome. Not only were a plethora of abstracts dedicated to individualized therapy but nearly all the advertisements employed this term and targeted therapy was emphasized in the press program.

Ignoring the centennial of World War I ignores that fact that targeting came into its own during that conflict. This was the first major conflict in which accuracy of artillery improved dramatically. Snipers were used more liberally than ever before, and long-range accuracy improved with weapons such as the "Big Bertha " howitzer and the "Paris Gun (in fact, the "Paris Gun" was not as accurate as advertised, but, nonetheless, was able to hurl projectiles from 120 kilometers away)." Note, however, that this was also the first large-scale conflict to use machine gun fire to blanket an area with bullets, and to disperse poison gas, which could devastate large segments of the enemy but could also drift back to affect the side of origin (ironically, mustard gas was the basis for the first effective chemotherapy agents) . Thus, there were major advances in both targeted and non-specific modalities. Needless to say, without both modalities, the war might never had ended and conflicts might still be going only somewhere in this world.

It is ironic that medical oncologists are overwhelmingly supportive of targeted therapy, but seem to hesitate to make full use of the original targeted therapy: radiation therapy. The limitation of radiation therapy is that it predominantly affects the immediate volume to which it is pointed, but that is also its appeal. Efforts to turn radiation therapy into systemic therapy have been only minimally successful, with the exception of certain applications of whole body irradiation and the use of radioisotopes, such as radium-223 dichloride, and antibody-bound isotopes such as ibritumomab tiuxetan. As radiation therapy techniques have allowed targets to be better identified and localized for treatment, the specialty has been rewarded by having its reimbursement lowered year after year, with the most targeted technique of all, brachytherapy, decreasing in availability and use because of particularly harsh cuts. At the same time, targeted systemic therapies are on the verge of bankrupting the medical care budget. Keep also in mind that the National Cancer Institute is funded with $4.923 billion this year, the vast majority of which is spent on developing and promoting systemic therapy. This leaves only two alternatives:

1. Do our best to promote the efficacy of our techniques to the public and to referring doctors, in the hope that the importance of radiation therapy can be remembered when limited health care dollars are distributed.

2. Eliminate the category of "radiation oncology" and consider what we do to be targeted therapy, give it every 28 days, and charge $7,000 for each cycle.